1. Field of the Invention
This invention relates to a device and a method for producing arrays of molecules, and more specifically, the invention relates to a device and a method for transporting specific molecules in a solution and precisely loading the molecules onto an array configuration while minimizing contamination.
2. Background of the Invention
Subjecting a specific reactant for analysis to an array of chemicals is accomplished in a myriad of ways. For many wet-bench analyses, wherein macroscopic quantities are utilized, a simple test tube rack or microwell plate is suitable. When microscopic quantities are manipulated, for example in forensic situations, micro-pipettes techniques are utilized. When very small quantities are handled, automated systems are required.
The use of arrays of oligonucleotides is known for oligonucleotide sequencing activities and allele detection. A myriad of ways for producing the arrays also is known, including U.S. Pat. No. 5,756,050, awarded to the instant Assignee on May 26, 1998, and U.S. Pat. No. 5,962,329, awarded to the instant Assignee on Oct. 5, 1999. Both patents are incorporated herein by reference.
Generally, a solution well is accessed via a small diameter pin wherein fluid adhesion causes an amount of fluid to attach to the pin for subsequent transfer to an absorbent array cell.
Several quality control drawbacks exist with present systems used to load arrays. First, inasmuch as extremely small amounts of oligo-solution are loaded at the end of the transfer pins, evaporation during initial pin loading or transfer occurs. Evaporation from the oligonucleotide supply wells also occurs, which can lead to a change in oligo-concentration ultimately loaded into array cells. And the potential for contamination of the wells exists due to ever-settling microscopic debris in the air. The above problems are exacerbated inasmuch as present systems lack the means for quickly and immediately assessing the degree to which the correct solutions are loaded onto a specific position on the array.
Another drawback with current configurations is the lack of precision caused by the inability to align the various components of the arraying system quickly and in real-time. Yet another drawback is the lack of a built-in ability to have a flexible system to respond to both adjustments in template design and in specific location of particular solutions or molecules on the loaded array.
As a result of the foregoing, oligo-pin loading and transfer operations must occur in humidity controlled environs and also in extremely clean environments. Also, the solution-loading and solution-transfer operations of state-of-the-art systems cannot deviate from a rigid template protocol. The lack of precision of current aligning equipment prevents solution loading onto microscopic sized arrays. As such, substantial duplication loadings of particular array regions are necessary.
Furthermore, despite the provision of such elaborate transfer rooms, quality control of the resulting oligo-loaded arrays also suffers due to mechanical anomalies of the transfer process. For instance, after only a few transfers, the extremely delicate transfer pins often bend, leading to cross contamination with neighboring array cells. Furthermore, the height of the pin tips may vary due to some pin lengths being either too long or short, resulting in inconsistent pin contact with matrix-cell locations. This inconsistency may deform the oligo-matrix contact points or cause in-complete loading of the oligo from the pin to the matrix cell.
A need exists in the art for a device and method for maintaining, confirming and documenting quality control of oligonucleotide-loading procedures onto a matrix. The device and method should obviate the need for elaborate environmental control requirements but be simple in design and operation. In addition, the device should be easy to maintain in a clean and precise working order.
It is an object of the present invention to provide a device and method for producing arrays of molecules that overcome many of the disadvantages of the prior art.
Another object of the present invention is a device for manufacturing arrays of molecules. A feature of the device is that an ultimate user can remotely operate the device and design the array. An advantage of the invention is the elimination of errors in processing customer orders and rapid turn-around of customer orders for customized biochips.
Still another object of the present invention is to provide a device for accurately transferring aqueous solutions from a reservoir to a position on a microscopic matrix. A feature of the invention is the utilization of a temperature controlled system and gravity-induced systems, the systems including an inverted oligonucleotide reservoir and a gravity fed-washing system. An advantage of the invention is that evaporation from the solution reservoir and solution transport vehicles is minimized, as is contamination of the reservoir from air-borne debris.
Another object of the present invention is to provide an automated method for producing micro arrays of molecules. A feature of the invention is the user""s active, on-line instruction in preparing the array via software driven robots. An advantage of the invention is the elimination of errors in processing customer orders and rapid turn around of the orders.
Yet another object of the present invention is to provide a method for transporting solutions, such as oligonucleotides in an aqueous mixture, from an oligonucleotide reservoir to a matrix. A feature of the invention is the utilization of gravity and capillary action to facilitate oligonucleotide loading and unloading from an oligo-transport vehicle. An advantage of the invention is the elimination of evaporation from the reservoir, the elimination of inadvertent contamination of the reservoir from ambient debris, and of elimination of positive pressure washing systems of the oligo-transport vehicle.
Another object of the present invention is to provide an automated method and device for transferring microscopic quantities of solution to microscopic array positions. A feature of the invention is the utilization of real-time quality control processes to monitor the adequacy of matrix cell loading. Another feature of the invention is the archiving of quality control images. An advantage of the invention is that the number of rejections of biochips due to improper loading are minimized. Another advantage is that archival information can be utilized by end-users to ascertain whether matrix image anomalies are due to cell loading histories or to the actual reactants being scrutinized.
Briefly, the invention provides a device for producing microscopic arrays of molecules, the device comprising a plurality of inverted cavities containing solutions; a means for extracting solutions from the inverted cavities; a means for depositing the extracted solutions onto an addressable location on a matrix; a means for verifying that the solutions are deposited onto the location on the matrix; and a means for storing the verification information so that the information can be subsequently retrieved.
Also provided is a process for producing -an array of nucleotides, the process comprising providing a plurality of inverted solution cavities, wherein each cavity contains an oligonucleotide solution having a different specific base sequence; extracting each oligonucleotide solution from the inverted cavity while the cavities are maintained in an inverted position; loading each oligonucleotide solution at a predetermined position in an array; and verifying that each oligonucleotide is loaded onto its respective position in the array.